Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines

摘要

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b(+) cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b(+) TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1 alpha pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1 alpha delayed growth of TAMC-induced tumors. Further analysis showed that IL-1 alpha inhibition led to decreased angiogenesis within tumors, suggesting that IL-1 alpha promotes prostate tumor progression, potentially through augmentation of angiogenesis.